Peptide fragmentation pathways

Electron transfer dissociation (ETD) is an ECD-like method with most of the same characteristics [21]. Like ECD, ETD yields abundant peptide backbone c- and z-type ions while often retaining such labile groups as peptide O/TV-glycosylation and phosphorylation [22]. Unlike ECD, ETD can be performed in the presence of an RF field. Here, anions created in a chemical ionization (Cl) source (see Section 2.1.7) are used as electron donors but the fragmentation pathways are essentially the same as for ECD. Commercial linear QIT instruments have recently become available with the ETD option. 

S. Muller, A. Hutson, V. Arya, G. Hochhaus, Assessment of Complex Peptide Degradation Pathways via Structured Multicompartmental Modeling Approaches The Metabolism of Dynorphin Al-13 and Related Fragments in Human Plasma , J. Pharm. Sci. 1999, 88, 938-944 S. Muller, G. Hochhaus, Metabolism of Dynorphin A 1-13 in Human Blood and Plasma , Pharm. Res. 1995, 12, 1165- 1170. 

Muller, S., A. Hutson,V. Arya, and G. Hochhaus. 1999. Assessment of complex peptide degradation pathways via structured multicompartmental modeling approaches the metabolism of dynorphin Al-13 and related fragments in human plasma [In Process Citation]. 

Interpretation of the spectra is based on the mechanisms and the fragmentation pathways described above, as shown by the following example. A CID MS/MS fragment spectrum of a peptide with sequence Gly-Ile-Pro-Thr-Leu-Leu-Leu-Phe-Lys measured at high energy is shown in Figure 8.13. This spectrum contains the complete series of b ions, thus allowing one to deduce the peptide sequence from the N-terminal acid to the C-terminal acid, whereas the series of y ions allows identification of the sequence in the reverse direction. In fact, the mass difference of 97 Da between peak b2 and b3 indicates that the amino acid in position 3 corresponds to a proline (see Table 8.2). Similarly, the 147 Da difference between peaks yi and y2 indicates that, the amino acid in the next-to-last position is a phenylalanine. The m/z values of ions W3, W4, W5 and wg imply that the amino acid in... 

Paizs B, Suhai S. Fragmentation pathways of protonated peptides. Mass Spectrom. Rev. 2005 24 508-548. 

Pyrolysis of a-amino acids has significant implications in the interpretation of the results of peptide and protein pyrolysis. Amino acid thermal decomposition takes place through four main fragmentation pathways as shown below ... 

Heparin has been used in enzyme purification such as recombinant human mast cell tryptase. The purified enzyme is fully active [12]. Heparin-based affinity chromatography also permitted the isolation of growth factors such as basic fibroblast growth factor (bFGF). The affinity is lower when bFGF is complexed with acidic gelatin [13]. The elution of synthetic TFPI (tissue factor pathway inhibitor) peptidic fragments on immobilized heparin has allowed one to find the peptidic sequence responsible for the TFPI-heparin interaction [14]. 

In a similar manner CD8+ T cells recognize peptide fragments displayed on MHC class I molecules. These fragments arise via a somewhat different pathway that forms fragments of viral proteins or proteins of other intracellular pathogens. Recognition by a CD8+ T cell usually converts it into a cytotoxic (killer) T cell, which will kill the infected This type of im-... 

Khossravi M, Borchardt R T (2000). Chemical pathways of peptide degradation. X Effect of metal catalyzed oxidation on the solntion strnctnre of a histidine-containing peptide fragment of hnman relaxin. Pharm. Res. 17 851-858. 

---